0000000000225242

AUTHOR

Christof Sohn

showing 9 related works from this author

A distinct subset of HLA-DR+-regulatory T cells is involved in the induction of preterm labor during pregnancy and in the induction of organ rejectio…

2010

Regulatory T cells (Tregs) are known to suppress alloimmune responses during pregnancy and post organ transplantation. We demonstrate that a distinct subset of FoxP3(+)DR(+)-Tregs among the total CD4(+)CD127(low+/-)CD25(+)-Treg cell pool is critically involved in preterm labor induction and kidney transplant rejection as well. Compared to healthy pregnancies and non-rejecting kidney recipients, we found that the percentage of the FoxP3(+)DR(+)-Treg subset was not reduced, but that the level of HLA-DR expression of such Tregs was strongly diminished in preterm laboring women and in patients with acute renal allograft rejection. In addition, both patient collectives showed a significantly red…

Graft RejectionMalemedicine.medical_specialtyImmunologychemical and pharmacologic phenomenaT-Lymphocytes RegulatoryOrgan transplantationImmune toleranceInterleukin-7 Receptor alpha SubunitObstetric Labor PrematurePregnancyT-Lymphocyte SubsetsHLA-DRImmune ToleranceImmunology and AllergyMedicineHumansKidney transplantationbusiness.industryInterleukin-2 Receptor alpha SubunitFOXP3hemic and immune systemsForkhead Transcription FactorsHLA-DR Antigensmedicine.diseaseKidney TransplantationTransplant rejectionCD4 Lymphocyte CountTransplantationTolerance inductionImmunologyPremature BirthFemalebusinessClinical immunology (Orlando, Fla.)
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The Presence of Gestational Diabetes is Associated with Increased Detection of Anti-HLA-class II Antibodies in the Maternal Circulation

2006

Problem Gestational diabetes (GD) may be associated with temporarily reduced immune tolerance toward alloantigens for the time of pregnancy. The aim of this study was to assess anti-HLA-class I and -II antibodies as markers for an aberrant immunostimulation in women with GD. Method of study The percentage of anti-HLA-class I and -II antibodies was estimated in women with GD, normal term delivery and fetal distress, which was confirmed by demonstrating low cord blood pH for this patient group. These antibodies may cross the placental barrier and cause interleukin-6 (IL-6) release from fetal monocytes by cross-linking monocytes with antibody-loaded cells. Therefore we estimated the percentage…

medicine.medical_specialtyImmunologyModels BiologicalFetal DistressAntigenIsoantibodiesPregnancyInternal medicinemedicineFetal distressHumansImmunology and AllergyFetusPregnancybusiness.industryHistocompatibility Antigens Class IIObstetrics and GynecologyHydrogen-Ion ConcentrationFetal Bloodmedicine.diseaseGestational diabetesDiabetes GestationalTolerance inductionFetal circulationEndocrinologyReproductive MedicineCord bloodLeukocytes MononuclearFemalebusinessAmerican Journal of Reproductive Immunology
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Small for gestational age (SGA) neonates show reduced suppressive activity of their regulatory T cells

2009

Little information exists concerning the role of fetal regulatory T cells (Tregs) during intrauterine development. We examined whether complications such as reduced birth weight or the occurrence of preterm labor were associated with deficiencies in the number or in the immunosuppressive activity of Tregs in the fetal circulation. Their total number did not change during normal or complicated pregnancy. In contrast, their level of FoxP3 expression decreased continuously with gestational age and was significantly reduced in the presence of spontaneous term, but not preterm labor. In small for gestational age (SGA) neonates, FoxP3 expression was constantly decreased when compared to age match…

medicine.medical_specialtyImmunologychemical and pharmacologic phenomenaCell SeparationT-Lymphocytes RegulatoryFetusObstetric Labor PrematurePregnancyT-Lymphocyte SubsetsInternal medicinemedicineHumansImmunology and AllergyPregnancyFetusbusiness.industryInfant NewbornGestational ageForkhead Transcription Factorshemic and immune systemsInfant Low Birth WeightFlow Cytometrymedicine.diseaseLow birth weightTolerance inductionEndocrinologyFetal circulationGestationSmall for gestational ageFemalemedicine.symptombusinessClinical Immunology
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Distinct subsets of regulatory T cells during pregnancy: is the imbalance of these subsets involved in the pathogenesis of preeclampsia?

2008

Abstract Regulatory T cells (CD4 + CD25 + FoxP3 + -Treg cells) are important regulators of tolerance induction during pregnancy. We now found that the number of CD4 + CD25 + FoxP3 + -Treg cells decreases during normal course of pregnancy and even more so in women affected by preeclampsia. The functional activity of these CD4 + CD25 + -Treg cells was significantly reduced in comparison to those of healthy pregnants. Further analysis revealed two Treg subsets that differed with regard to the FoxP3 and CD25 expression. The percentage of both, CD4 + CD25 + FoxP3 high+ -Treg and CD4 + CD25 high+ FoxP3 + , was maximal in the first and second trimenon, but declined severely in the third trimenon. …

medicine.medical_specialtyHELLP SyndromeImmunologyPopulationchemical and pharmacologic phenomenaBiologyT-Lymphocytes RegulatoryImmune tolerancePreeclampsiaPathogenesisPre-EclampsiaPregnancyT-Lymphocyte SubsetsInternal medicinemedicineImmunology and AllergyHumansIL-2 receptoreducationeducation.field_of_studyInterleukin-2 Receptor alpha SubunitFOXP3hemic and immune systemsForkhead Transcription FactorsT lymphocytemedicine.diseaseFlow CytometryCoculture TechniquesTolerance inductionEndocrinologyImmunologyFemaleClinical immunology (Orlando, Fla.)
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Pregnancy-associated diseases are characterized by the composition of the systemic regulatory T cell (Treg) pool with distinct subsets of Tregs

2011

Dysregulations concerning the composition and function of regulatory T cells (T(regs)) are assumed to be involved in the pathophysiology of complicated pregnancies. We used six-colour flow cytometric analysis to demonstrate that the total CD4(+) CD127(low+/-) CD25(+) forkhead box protein 3 (FoxP3)(+) T(reg) cell pool contains four distinct T(reg) subsets: DR(high+) CD45RA(-), DR(low+) CD45RA(-), DR(-) CD45RA(-) T(regs) and naive DR(-) CD45RA(+) T(regs). During the normal course of pregnancy, the most prominent changes in the composition of the total T(reg) cell pool were observed between the 10th and 20th weeks of gestation, with a clear decrease in the percentage of DR(high+) CD45RA(-) and…

AdultHELLP Syndromemedicine.medical_specialtyTranslational StudiesRegulatory T cellImmunologyGestational Agechemical and pharmacologic phenomenaT-Lymphocytes RegulatoryImmunophenotypingFlow cytometryObstetric Labor PrematureImmunophenotypingPre-EclampsiaPregnancyT-Lymphocyte Subsetsimmune system diseaseshemic and lymphatic diseasesInternal medicinemedicineHomeostasisHumansImmunology and AllergyIL-2 receptorInterleukin-7 receptormedicine.diagnostic_testbusiness.industryvirus diseasesFOXP3hemic and immune systemsFlow CytometryCoculture TechniquesPathophysiologyEndocrinologymedicine.anatomical_structureCervical Length MeasurementImmunologyLeukocyte Common AntigensFemaleUterine Cervical IncompetencebusinessHomeostasisClinical and Experimental Immunology
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The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus.

2014

Physiological changes during normal pregnancy are characterized by an inflammatory immune response and insulin resistance. Therefore, we hypothesize that gestational diabetes mellitus (GDM) may be caused by an inappropriate adaption of the maternal immune system to pregnancy. In this study we examined the role of regulatory T cell (Treg) differentiation for the development of GDM during pregnancy. We used six-colour flow cytometric analysis to demonstrate that the total CD4(+) CD127(low+/-) CD25(+) forkhead box protein 3 (FoxP3(+)) T(reg) pool consists of four different T(reg) subsets: naive CD45RA(+) T(regs), HLA-DR(-) CD45RA(-) memory T(regs) (DR(-) T(regs)) and the highly differentiated …

Adultmedicine.medical_specialtyendocrine system diseasesRegulatory T cellImmunologychemical and pharmacologic phenomenaCell SeparationLymphocyte ActivationT-Lymphocytes RegulatoryImmunophenotypingYoung AdultImmune systemInsulin resistanceimmune system diseasesPregnancyT-Lymphocyte Subsetshemic and lymphatic diseasesInternal medicinemedicineImmune ToleranceImmunology and AllergyHomeostasisHumansIL-2 receptorInterleukin-7 receptorbusiness.industryFOXP3hemic and immune systemsCell DifferentiationForkhead Transcription FactorsT helper cellOriginal Articlesmedicine.diseaseFlow CytometryGestational diabetesDiabetes GestationalEndocrinologymedicine.anatomical_structureImmunologyCD4 AntigensFemalebusinessImmunologic MemoryClinical and experimental immunology
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Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

2013

Journal article TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ~480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10!-7), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10!-8) and BRCA1 mutation carrier (P = 1.1 × 10!-5) breast cancers and altered promot…

TelomeraseMessengerCàncer d'ovariEstrogen receptorAetiology screening and detection [ONCOL 5]0302 clinical medicineBreast cancerRisk FactorsAlternative Splicing; Biomarkers Tumor; Breast Neoplasms; Case-Control Studies; Chromatin; DNA Methylation; Female; Gene Expression Profiling; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Luciferases; Oligonucleotide Array Sequence Analysis; Ovarian Neoplasms; Polymorphism Single Nucleotide; RNA Messenger; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Telomerase; Telomere; GeneticsGenotypeBUCCAL CELLSLuciferasesTelomeraseOligonucleotide Array Sequence AnalysisOvarian Neoplasms0303 health sciencesTumorTelòmerReverse Transcriptase Polymerase Chain ReactionGENETIC-VARIATIONCOMMON VARIANTSSingle Nucleotidetert-clptm1l locus; genome-wide association; genetic-variation; susceptibility loci; buccal cells; fibroblasts; common variants; carcinoma; reverse-transcriptase htert; metaanalysisTelomereAetiology screening and detection Immune Regulation [ONCOL 5]Chromatin3. Good healthTumor Markers Biological030220 oncology & carcinogenesisFemaleFIBROBLASTSGenotypeSUSCEPTIBILITY LOCICARCINOMASingle-nucleotide polymorphismBreast NeoplasmsBiologyReal-Time Polymerase Chain ReactionPolymorphism Single NucleotideArticleCàncer de mama03 medical and health sciencesBreast cancerSDG 3 - Good Health and Well-beingTranslational research [ONCOL 3]Ovarian cancermedicineGeneticsBiomarkers TumorHumansGenetic Predisposition to DiseaseRNA MessengerPolymorphismAlleleGENOME-WIDE ASSOCIATIONMETAANALYSIS030304 developmental biologyMolecular epidemiology Aetiology screening and detection [NCEBP 1]Breast cancer susceptibilityHereditary cancer and cancer-related syndromes [ONCOL 1]Translational research Genomic disorders and inherited multi-system disorders [ONCOL 3]Gene Expression ProfilingDNA Methylationmedicine.diseaseMolecular biologyTERT-CLPTM1L LOCUSTelomereMinor allele frequencyAlternative SplicingGenetic LociCase-Control StudiesRNABiomarkersREVERSE-TRANSCRIPTASE HTERTGenome-Wide Association StudyNature genetics
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Genome-wide association studies identify four ER negative-specific breast cancer risk loci

2013

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environm…

Oncologygenetic associationbody-mass indexEstrogen receptorGenome-wide association studycancer riskBioinformaticssusceptibilitychromosome 1q0302 clinical medicineRisk Factorssingle nucleotide polymorphismGenotypeestrogenCooperative Behaviorcomparative studyOligonucleotide Array Sequence Analysis0303 health scienceschromosome 16q3. Good healthReceptors Estrogenpriority journal030220 oncology & carcinogenesisFemalecancer invasionsignal transductionbreast cancer; cancer invasion; cancer risk; chromosome 1; chromosome 16q; chromosome 1q; chromosome 2p; comparative study; follow up; gene locus; genetic association; genetic susceptibility; human; nucleotide sequence; priority journal; signal transduction; single nucleotide polymorphismmedicine.medical_specialtyGenotypegene locusBreast NeoplasmsSingle-nucleotide polymorphismBiologyPolymorphism Single NucleotideArticle03 medical and health sciencesBreast cancerbreast cancerMeta-Analysis as TopicSDG 3 - Good Health and Well-beingInternal medicineexpressionGeneticsmedicineGenetic predispositionHumansfollow upGenetic Predisposition to Diseasehumanchromosome 1gene030304 developmental biologyCase-control studyCancernucleotide sequencemedicine.diseasechromosome 2pGenetic LociCase-Control Studiescommon variantGenome-Wide Association Studygenetic susceptibilityNature Genetics
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A low-frequency haplotype spanning SLX4/FANCP constitutes a new risk locus for early-onset breast cancer (<60 years) and is associated with reduce…

2017

Only a fraction of breast cancer (BC) cases can be yet explained by mutations in genes or genomic variants discovered in linkage, genome-wide association and sequencing studies. The known genes entailing medium or high risk for BC are strongly enriched for a function in DNA double strand repair. Thus, aiming at identifying low frequency variants conferring an intermediate risk, we here investigated 17 variants (MAF: 0.01-0.1) in 10 candidate genes involved in DNA repair or cell cycle control. In an exploration cohort of 437 cases and 1189 controls, we show the variant rs3810813 in the SLX4/FANCP gene to be significantly associated with both BC (≤60 years; OR = 2.6(1.6-3.9), p = 1.6E-05) and…

0301 basic medicineGeneticsCancer ResearchCandidate geneHaplotypeLocus (genetics)Single-nucleotide polymorphismBiologyPenetrance03 medical and health sciences030104 developmental biologyOncologyAlleleAllele frequencyImputation (genetics)International Journal of Cancer
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